The characteristics of proteins and enzymes in living systems derive not only from structural genes, but also from the expression of accessory genetic elements, such as the regulatory genes of bacteria. Well-documented examples of such elements in animal systems are unknown. However, mutations have been described in mice and in humans whose properties conform to genetic factors controlling the subcellular localization, temporal accumulation, rate of synthesis and rate of degradation of specific enzymes. The principal objective of the proposed research is to gain an understanding of genetic control mechanisms which underly the expression of enzymes in animal cells. This objective will be pursued by genetic and biochemical analyses of mutations which alter the expression of murine glucuronidase. Among the specific objectives are: (1) to characterize a genetic change in the structure of murine glucuronidase; (2) to relate the change in structur of glucuronidase to other phenotypic alteration in glucuronidase expression; (3) to analyze the relationship between lysosomal and microsomal glucuronidase; and (4) to analyze and exploit the genetic alterations in the androgen inducibility of kidney glucuronidase as a probe into the genetic control of enzyme regultory mechanisms of mammalian cells.